Rumeysa DUYURAN, Demet TAŞDEMİR, Pınar YUMRUTAŞ, Hülya GÜVEN, Nurevşan KUŞDOĞAN, Zeynep Sav TUNCA, Serdar ÖZTUZCU, Esra BOZGEYİK, Ahmet Ferudun IŞIK, Ahmet ULUSAN, Hülya ÇİÇEK, İbrahim BOZGEYİK
European Journal of Therapeutics - 2026;32(3):281-289
Objective: Amphiregulin (AREG), which is known as a ligand for the epidermal growth factor receptor (EGFR), is widely expressed by cancerous and immune cells . By activating EGFR signaling, AREG enhances GLUT1 expression. It also promotes intracellular glucose uptake. In this way it supports glycolysis and lactate production. This metabolic hallmark is known as the Warburg effect. A similar glycolytic shift occurs in activated natural killer (NK) cells, which are essential components of antiviral and antitumor immunity. The aim of this study is to investigate the relationship between serum AREG levels and NK cell activation in patients with non-small cell lung cancer (NSCLC). Methods: This is a case-control study which includes 40 NSCLC patients and 40 healthy controls. Serum AREG levels were measured by ELISA and NK cell activation was assessed by using flow cytometric analysis of CD107a, CD69, CD314 (NKG2D), and CD337 (NKp30) parameters. Results: Serum AREG levels were significantly lower in NSCLC patients compared to healthy individuals. Although the overall percentage of NK cells was increased in patients, expression of activation markers especially CD107a was reduced . Correlation analysis revealed weak negative associations between AREG levels and expression of CD107a, CD69, CD314, and CD337. Conclusion: Collectively, these findings suggest that reduced serum AREG levels may be linked to impaired NK cell activation in NSCLC, potentially through limited glucose uptake, highlighting AREG as a potential regulator of immune metabolism and a candidate for further investigation in tumor immune evasion .
